The objective of the proposed experiments is to investigate the role of magnesium deficiency in the etiology of sedative-hypnotic physical dependence as manifested in the withdrawal syndrome. Mice made physically dependent on phenobarbital, diazepam, meprobamate or alcohol will be assessed for magnesium loss and investigations conducted into the mechanisms responsible for the loss. Studies aimed at pinpointing the anatomical and subcellular localization of the magnesium deficit in the brain will also be performed. The use of magnesium salts as a therapeutic intervention will also be explored experimentally in order to elucidate the optimal conditions (dose, route of administration, time of administration) for reducing the severity of withdrawal symptoms in physically dependent animals.